Racemic crystallography

Once the chemical synthesis of an L-protein is achieved, the D-protein enantiomer can be manufactured using synthetic peptide building blocks made from D-amino acids and Gly.

[1] Convergent synthesis is most effective in preparing long polypeptide chains, by using peptide-hydrazides, where the hydrazide can be converted to a thioester for use in native chemical ligation.

The remaining 165 space groups contain either a center of symmetry or a mirror plane and are thus not accessible to natural globular proteins, which are chiral molecules.

They suggested the preferred space group was determined by the number of degrees of freedom (D) or dimensionality as a measure of the ease with which a given symmetry can be formed.

[1] In 1989, Alan Mackay suggested that if chemical synthesis could be used to make L-protein and D-protein enantiomers, it would enable the use of racemic mixtures to crystallize proteins in centrosymmetric space groups.

This was done since the structural determination would potentially be easier and more robust by using diffraction data from a centrosymmetric crystal, which requires growth from a racemic mixture.

In the course of that work it was observed that racemic and even quasi-racemic protein mixtures dramatically facilitated the formation of diffraction quality, centrosymmetric crystals.

[4] Interestingly, achiral "'peptoid'" chains were found to fold as racemic pairs and crystallize in highly preferred centrosymmetric space groups.